Domain-knowledge enabled ensemble learning of 5-formylcytosine (f5C) modification sites.

5-formylcytidine (f5C) is a unique post-transcriptional RNA modification found in mRNA and tRNA at the wobble site, playing a crucial role in mitochondrial protein synthesis and potentially contributing to the regulation of translation. Recent studies have unveiled that the f5C modifications may drive mitochondrial mRNA translation to power cancer metastasis. Accurate identification of f5C sites is essential for further unraveling their molecular functions and regulatory mechanisms, but there are currently no computational methods available for predicting their locations. In this study, we introduce an innovative ensemble approach, successfully enabling the computational recognition of Saccharomyces cerevisiae f5C. We conducted a comprehensive model selection process that involved multiple basic machine learning and deep learning algorithms such as recurrent neural networks, convolutional neural networks and Transformer-based models. Initially trained only on sequence information, these individual models achieved an AUROC ranging from 0.7104 to 0.7492. Through the integration of 32 novel domain-derived genomic features, the performance of individual models has significantly improved to an AUROC between 0.7309 and 0.8076. To further enhance accuracy and robustness, we then constructed the ensembles of these individual models with different combinations. The best performance attained by our ensemble models reached an AUROC of 0.8391. Shapley additive explanations were conducted to explain the significant contributions of genomic features, providing insights into the putative distribution of f5C across various topological regions and potentially paving the way for revealing their functional relevance within distinct genomic contexts. A freely accessible web server that allows real-time analysis of user-uploaded sites can be accessed at: www.rnamd.org/Resf5C-Pred.

Breaking the Linear Scaling Relationship by Alloying Micro Sn to a Cu Surface toward CO2 Electrochemical Reduction.

The electrochemical CO2 reduction reaction (CO2RR) to HCOOH provides an avenue for reducing global accelerated CO2 emissions and producing high-value-added chemicals. Nevertheless, the presence of an inherent linear scaling relationship (LSR) between *OCHO and *HCOOH leads to the electrosynthesis of HCOOH being achieved at high cathodic potentials. In this work, by adjusting the different Cu:Sn ratio of SnxCu(1-x) alloys, we comprehensively explored the electrocatalytic 2e- CO2RR performance toward the production of HCOOH. Combining density functional theory calculations with the constant-potential implicit solvent model, the Sn0.03Cu0.97 surface alloy was posited to be a promising electrocatalyst with superior HCOOH selectivity and an ultralow limiting potential of -0.20 V in an environment of pH = 7.2. The high performance was found to originate from the breaking of the LSR, which is a result of an extraordinary electronic property of the active Cu site. This work not only advances a global-searched strategy for the rational design of efficient catalysts toward HCOOH production but also provides in-depth insights into the underlying mechanism for the enhanced performance of microalloy electrocatalysts.

Electrochemical Urea Production over Diatomic Fe-Ni Catalyst: a Mechanism for C-N Coupling.

Co-electrocatalytic reduction of CO2 and nitrate/nitrite as carbon and nitrogen sources to synthesize urea is an effective strategy to solve the energy problem and alleviate environmental pollution. In this work, combined density functional theory calculations with a constant-potential implicit solvent model, we proposed a strategy for the determination of the preferred reaction pathway and the potential window that is guided by the potential-dependent free energy change. It was found that on the FeNi-N6-C surface, the C-N coupling occurs between *NHO and the protonated CO2 in the potential window of -2.43 to -1.34 V for the urea electrochemical production, where the predicted onset potential accords well with the experimental results. The activity originates from the less weak bonding strength of N-O and the negatively charged N atom in *NHO. This study offers a general approach to determining the optimal reaction pathway in electrochemistry and insights into the mechanism of electrochemical synthesis of urea.

Deciphering recursive polyploidization in Lamiales and reconstructing their chromosome evolutionary trajectories.

Lamiales is an order of core eudicots with abundant diversity, and many Lamiales plants have important medicinal and ornamental values. Here, we comparatively reanalyzed 11 Lamiales species with well-assembled genome sequences and found evidence that Lamiales plants, in addition to a hexaploidization or whole-genome triplication (WGT) shared by core eudicots, experienced further polyploidization events, establishing new groups in the order. Notably, we identified a whole-genome duplication (WGD) occurred just before the split of Scrophulariaceae from the other Lamiales families, such as Acanthaceae, Bignoniaceae, and Lamiaceae, suggesting its likely being the causal reason for the establishment and fast divergence of these families. We also found that a WGT occurred ∼68 to 78 million years ago (Mya), near the split of Oleaceae from the other Lamiales families, implying that it may have caused their fast divergence and the establishment of the Oleaceae family. Then, by exploring and distinguishing intra- and intergenomic chromosomal homology due to recursive polyploidization and speciation, respectively, we inferred that the Lamiales ancestral cell karyotype had 11 proto-chromosomes. We reconstructed the evolutionary trajectories from these proto-chromosomes to form the extant chromosomes in each Lamiales plant under study. We must note that most of the inferred 11 proto-chromosomes, duplicated during a WGD thereafter, have been well preserved in jacaranda (Jacaranda mimosifolia) genome, showing the credibility of the present inference implementing a telomere-centric chromosome repatterning model. These efforts are important to understand genome repatterning after recursive polyploidization, especially shedding light on the origin of new plant groups and angiosperm cell karyotype evolution.

m6A-TCPred: a web server to predict tissue-conserved human m6A sites using machine learning approach.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic cells that plays a crucial role in regulating various biological processes, and dysregulation of m6A status is involved in multiple human diseases including cancer contexts. A number of prediction frameworks have been proposed for high-accuracy identification of putative m6A sites, however, none have targeted for direct prediction of tissue-conserved m6A modified residues from non-conserved ones at base-resolution level. RESULTS: We report here m6A-TCPred, a computational tool for predicting tissue-conserved m6A residues using m6A profiling data from 23 human tissues. By taking advantage of the traditional sequence-based characteristics and additional genome-derived information, m6A-TCPred successfully captured distinct patterns between potentially tissue-conserved m6A modifications and non-conserved ones, with an average AUROC of 0.871 and 0.879 tested on cross-validation and independent datasets, respectively. CONCLUSION: Our results have been integrated into an online platform: a database holding 268,115 high confidence m6A sites with their conserved information across 23 human tissues; and a web server to predict the conserved status of user-provided m6A collections. The web interface of m6A-TCPred is freely accessible at: www.rnamd.org/m6ATCPred .

Expansion of apple cultivation increases the abundance of codling moth (Cydia pomonella) in agricultural landscapes of China.

BACKGROUND: Agricultural land-use change is an important driver of pest population dynamics, and can alter source-sink dynamics and the concentration-dilution effects of the landscape. Understanding the effects of land use on pests at both landscape and regional levels is essential for the development of sustainable pest management strategies given the large changes occurring in cropping systems in China. At the landscape level, we investigated the impacts of landscape composition and edge density on pheromone trap catch of codling moth (Cydia pomonella) in apple orchards, in Aksu, Xinjiang, China. At the regional scale, we conducted a meta-analysis using data from studies performed across the Aksu area in recent decades, to assess the relationship between trends in codling moth abundance and the area of apple cultivation. RESULTS: Both extensive planting of apple and large areas of annual crops in the landscape increased the abundance of codling moth, whereas the presence of secondary host plants (peach, pear, walnut, plum, and apricot) had a negative effect. Seminatural habitats and landscape edge density did not significantly affect codling moth abundance. The responses of different generations of codling moth to landscape factors were varied. At the regional level, codling moth occurrence was positively correlated with the expansion of apple production areas. CONCLUSION: Expansion of apple cultivation increases the abundance of codling moth in agricultural landscapes. We recommend decreasing the area devoted to monocultures of apple when designing agricultural landscapes and increasing plantings of secondary host crops to dilute and reduce the abundance of codling moth. © 2024 Society of Chemical Industry.

Realizing multiferroics in α-Ga2S3via hole doping: a first-principles study.

Using first-principles calculations, we report the realization of multiferroics in an intrinsic ferroelectric α-Ga2S3 monolayer. Our results show that the presence of intrinsic gallium vacancies, which is the origin of native p-type conductivity, can simultaneously introduce a ferromagnetic ground state and a spontaneous out-of-plane polarization. However, the high switching barrier and thermodynamic irreversibility of the ferroelectric reversal path disable the maintenance of ferroelectricity, suggesting that the defect-free form should be a prerequisite for Ga2S3 to be multiferroic. Through applying strain, the behavior of spontaneous polarization of the pristine α-Ga2S3 monolayer can be effectively regulated, but the non-magnetic ground state does not change. Strikingly, via an appropriate concentration of hole doping, stable ferromagnetism with a high Curie temperature and robust ferroelectricity can be concurrently introduced in the α-Ga2S3 monolayer. Our work provides a feasible method for designing 2D multiferroics with great potential in future device applications.

Precise Engineering of the Electrocatalytic Activity of FeN4-Embedded Graphene on Oxygen Electrode Reactions by Attaching Electrides.

Using first-principles calculations combined with a constant-potential implicit solvent model, we comprehensively studied the activity of oxygen electrode reactions catalyzed by electride-supported FeN4-embedded graphene (FeN4Cx). The physical quantities in FeN4Cx/electrides, i.e., work function of electrides, interlayer spacing, stability of heterostructures, charge transferred to Fe, d-band center of Fe, and adsorption free energy of O, are highly intercorrelated, resulting in activity being fully expressed by the nature of the electrides themselves, thereby achieving a precise modulation in activity by selecting different electrides. Strikingly, the FeN4PDCx/Ca2N and FeN4PDCx/Y2C systems maintain a high oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) activity with the overpotential less than 0.46 and 0.62 V in a wide pH range. This work provides an effective strategy for the rational design of efficient bifunctional catalysts as well as a model system with a simple activity-descriptor, helping to realize significant advances in energy devices.

Tissue-specific RNA methylation prediction from gene expression data using sparse regression models.

N6-methyladenosine (m6A) is a highly prevalent and conserved post-transcriptional modification observed in mRNA and long non-coding RNA (lncRNA). Identifying potential m6A sites within RNA sequences is crucial for unraveling the potential influence of the epitranscriptome on biological processes. In this study, we introduce Exp2RM, a novel approach that formulates single-site-based tissue-specific elastic net models for predicting tissue-specific methylation levels utilizing gene expression data. The resulting ensemble model demonstrates robust predictive performance for tissue-specific methylation levels, with an average R-squared value of 0.496 and a median R-squared value of 0.482 across all 22 human tissues. Since methylation distribution varies among tissues, we trained the model to incorporate similar patterns, significantly improves accuracy with the median R-squared value increasing to 0.728. Additonally, functional analysis reveals Exp2RM's ability to capture coefficient genes in relevant biological processes. This study emphasizes the importance of tissue-specific methylation distribution in enhancing prediction accuracy and provides insights into the functional implications of methylation sites.

Theoretical and Experimental Investigation of Surface Textures in Vibration-Assisted Micro Milling.

Vibration-assisted micro milling is a promising technique for fabricating engineered mi-cro-scaled surface textures. This paper presents a novel approach for theoretical modeling of three-dimensional (3D) surface textures produced by vibration-assisted micro milling. The proposed model considers the effects of tool edge geometry, minimum uncut chip thickness (MUCT), and material elastic recovery. The surface texture formation under different machining parameters is simulated and analyzed through mathematical modeling. Two typical surface morphologies can be generated: wave-type and fish scale-type textures, depending on the phase difference between tool paths. A 2-degrees-of-freedom (2-DOF) vibration stage is also developed to provide vibration along the feed and cross-feed directions during micro-milling process. Micro-milling experiments on copper were carried out to verify the ability to fabricate controlled surface textures using the vibration stage. The simulated and experimentally generated surfaces show good agreement in geometry and dimensions. This work provides an accurate analytical model for vibration-assisted micro-milling surface generation and demonstrates its feasibility for efficient, flexible texturing.

m6A-Atlas v2.0: updated resources for unraveling the N6-methyladenosine (m6A) epitranscriptome among multiple species.

N 6-Methyladenosine (m6A) is one of the most abundant internal chemical modifications on eukaryote mRNA and is involved in numerous essential molecular functions and biological processes. To facilitate the study of this important post-transcriptional modification, we present here m6A-Atlas v2.0, an updated version of m6A-Atlas. It was expanded to include a total of 797 091 reliable m6A sites from 13 high-resolution technologies and two single-cell m6A profiles. Additionally, three methods (exomePeaks2, MACS2 and TRESS) were used to identify >16 million m6A enrichment peaks from 2712 MeRIP-seq experiments covering 651 conditions in 42 species. Quality control results of MeRIP-seq samples were also provided to help users to select reliable peaks. We also estimated the condition-specific quantitative m6A profiles (i.e. differential methylation) under 172 experimental conditions for 19 species. Further, to provide insights into potential functional circuitry, the m6A epitranscriptomics were annotated with various genomic features, interactions with RNA-binding proteins and microRNA, potentially linked splicing events and single nucleotide polymorphisms. The collected m6A sites and their functional annotations can be freely queried and downloaded via a user-friendly graphical interface at: http://rnamd.org/m6a.

m7GHub V2.0: an updated database for decoding the N7-methylguanosine (m7G) epitranscriptome.

With recent progress in mapping N7-methylguanosine (m7G) RNA methylation sites, tens of thousands of experimentally validated m7G sites have been discovered in various species, shedding light on the significant role of m7G modification in regulating numerous biological processes including disease pathogenesis. An integrated resource that enables the sharing, annotation and customized analysis of m7G data will greatly facilitate m7G studies under various physiological contexts. We previously developed the m7GHub database to host mRNA m7G sites identified in the human transcriptome. Here, we present m7GHub v.2.0, an updated resource for a comprehensive collection of m7G modifications in various types of RNA across multiple species: an m7GDB database containing 430 898 putative m7G sites identified in 23 species, collected from both widely applied next-generation sequencing (NGS) and the emerging Oxford Nanopore direct RNA sequencing (ONT) techniques; an m7GDiseaseDB hosting 156 206 m7G-associated variants (involving addition or removal of an m7G site), including 3238 disease-relevant m7G-SNPs that may function through epitranscriptome disturbance; and two enhanced analysis modules to perform interactive analyses on the collections of m7G sites (m7GFinder) and functional variants (m7GSNPer). We expect that m7Ghub v.2.0 should serve as a valuable centralized resource for studying m7G modification. It is freely accessible at: www.rnamd.org/m7GHub2.

m5U-GEPred: prediction of RNA 5-methyluridine sites based on sequence-derived and graph embedding features.

5-Methyluridine (m5U) is one of the most common post-transcriptional RNA modifications, which is involved in a variety of important biological processes and disease development. The precise identification of the m5U sites allows for a better understanding of the biological processes of RNA and contributes to the discovery of new RNA functional and therapeutic targets. Here, we present m5U-GEPred, a prediction framework, to combine sequence characteristics and graph embedding-based information for m5U identification. The graph embedding approach was introduced to extract the global information of training data that complemented the local information represented by conventional sequence features, thereby enhancing the prediction performance of m5U identification. m5U-GEPred outperformed the state-of-the-art m5U predictors built on two independent species, with an average AUROC of 0.984 and 0.985 tested on human and yeast transcriptomes, respectively. To further validate the performance of our newly proposed framework, the experimentally validated m5U sites identified from Oxford Nanopore Technology (ONT) were collected as independent testing data, and in this project, m5U-GEPred achieved reasonable prediction performance with ACC of 91.84%. We hope that m5U-GEPred should make a useful computational alternative for m5U identification.

Compressed single-shot 3D photoacoustic imaging with a single-element transducer.

Three-dimensional (3D) photoacoustic imaging (PAI) can provide rich information content and has gained increasingly more attention in various biomedical applications. However, current 3D PAI methods either involves pointwise scanning of the 3D volume using a single-element transducer, which can be time-consuming, or requires an array of transducers, which is known to be complex and expensive. By utilizing a 3D encoder and compressed sensing techniques, we develop a new imaging modality that is capable of single-shot 3D PAI using a single-element transducer. The proposed method is validated with phantom study, which demonstrates single-shot 3D imaging of different objects and 3D tracking of a moving object. After one-time calibration, while the system could perform single-shot 3D imaging for different objects, the calibration could remain effective over 7 days, which is highly beneficial for practical translation. Overall, the experimental results showcase the potential of this technique for both scientific research and clinical applications.

Recombinant Porcine Interferon-α Decreases Pseudorabies Virus Infection.

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate immune system, which can effectively cure acute infectious diseases. Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). The clinical symptoms of PRV are as follows: reproductive dysfunction among pregnant sows and high mortality rates among piglets. These pose a severe threat to the swine industry. Related studies show that IFN-α has broad applications in preventing and treating viral diseases. Therefore, a PRV mouse model using artificial infection was established in this study to explore the pathogenic effect of IFN-α on PRV. We designed a sequence with IFN-α4 (M28623, Genbank) and cloned it on the lentiviral vector. CHO-K1 cells were infected and identified using WB and RT-PCR; a CHO-K1 cell line with a stable expression of the recombinant protein PoIFN-α was successfully constructed. H&E staining and virus titer detection were used to investigate the recombinant protein PoIFN-α's effect on PR in BALB/c mice. The results show that the PoIFN-α has a preventive and therapeutic impact on PR. In conclusion, the recombinant protein can alleviate symptoms and reduce the replication of PRV in vivo.

Gallium arsenide optical phased array photonic integrated circuit.

A 16-channel optical phased array is fabricated on a gallium arsenide photonic integrated circuit platform with a low-complexity process. Tested with a 1064 nm external laser, the array demonstrates 0.92° beamwidth, 15.3° grating-lobe-free steering range, and 12 dB sidelobe level. Based on a reverse biased p-i-n structure, component phase modulators are 3 mm long with DC power consumption of less than 5 µW and greater than 770 MHz electro-optical bandwidth. Separately fabricated 4-mm-long phase modulators based on the same structure demonstrate single-sided Vπ·L modulation efficiency ranging from 0.5 V·cm to 1.22 V·cm when tested at wavelengths from 980 nm to 1360 nm.

Electric Double Layer Based Epidermal Electronics for Healthcare and Human-Machine Interface.

Epidermal electronics, an emerging interdisciplinary field, is advancing the development of flexible devices that can seamlessly integrate with the skin. These devices, especially Electric Double Layer (EDL)-based sensors, overcome the limitations of conventional electronic devices, offering high sensitivity, rapid response, and excellent stability. Especially, Electric Double Layer (EDL)-based epidermal sensors show great potential in the application of wearable electronics to detect biological signals due to their high sensitivity, fast response, and excellent stability. The advantages can be attributed to the biocompatibility of the materials, the flexibility of the devices, and the large capacitance due to the EDL effect. Furthermore, we discuss the potential of EDL epidermal electronics as wearable sensors for health monitoring and wound healing. These devices can analyze various biofluids, offering real-time feedback on parameters like pH, temperature, glucose, lactate, and oxygen levels, which aids in accurate diagnosis and effective treatment. Beyond healthcare, we explore the role of EDL epidermal electronics in human-machine interaction, particularly their application in prosthetics and pressure-sensing robots. By mimicking the flexibility and sensitivity of human skin, these devices enhance the functionality and user experience of these systems. This review summarizes the latest advancements in EDL-based epidermal electronic devices, offering a perspective for future research in this rapidly evolving field.

Pseudouridine Identification and Functional Annotation with PIANO.

Pseudouridine (Ψ) is the first-discovered RNA modification abundantly present in many classes of RNAs, which plays a pivotal role in a series of biological processes. Accurately identifying the location of Ψ sites is helpful for relevant downstream researches. In this chapter, we introduce a website PIANO-for pseudouridine site (Ψ) identification and functional annotation, which enables researchers to predict human putative Ψ sites with a high-accuracy (average AUC of 0.955 under the full transcript model and 0.838 under the mature mRNA model when testing on six independent datasets). The posttranscriptional regulatory mechanisms of putative Ψ sites including miRNA-targets, RBP-binding regions, and splicing sites were also annotated. A comprehensive query database was also provided to deposit over 4300 human Ψ modifications, which is currently the most complete collection of experimental-derived Ψ sites. The PIANO website is freely accessible at: http://piano.rnamd.com or http://180.208.58.19/Ψ-WHISTLE .

Platelet-Rich Plasma Injections for Shoulder Adhesive Capsulitis Are at Least Equivalent to Corticosteroid or Saline Solution Injections: A Systematic Review of Prospective Cohort Studies.

PURPOSE: To evaluate the role of platelet-rich plasma (PRP) for adhesive capsulitis (AC) as compared with other injectables. METHODS: A literature search of the PubMed and Embase online databases was performed to identify articles evaluating injection therapy for the treatment of AC. The inclusion criteria included prospective studies comparing PRP against alternative injectables with a minimum of 15 patients in each treatment arm and a minimum 12-week follow-up period. Pain scores, range of motion, and function scores were the primary outcomes assessed. RESULTS: Five articles comparing PRP with corticosteroid or saline solution injections met the inclusion criteria. A total of 157 patients were treated with PRP, with a follow-up duration ranging from 3 to 6 months. All 5 studies showed statistically significant improvements in pain scores, motion, and function scores in patients receiving PRP, corticosteroid, and saline solution injections. However, PRP was consistently superior on intergroup analyses in all but 1 study. In 4 studies, pain and function scores favored PRP over control at final follow-up (range in mean difference, -2.2 to 0.69 for visual analog scale pain score [n = 5] and -50.5 to -4.0 for Shoulder Pain and Disability Index score [n = 3]), whereas 3 studies found greater improvement in shoulder motion after PRP (range in mean difference, 0.7° to 34.3° for forward flexion and -2.3° to 20.4° for external rotation [n = 4]). One study found no significant difference between PRP and corticosteroid injections but noted that the results were comparable. CONCLUSIONS: According to a limited number of prospective studies, PRP injections for AC are at least equivalent to corticosteroid or saline solution injections and often lead to improved pain, motion, and functional outcomes at 3- to 6-month follow-up. Given the small number of studies, with design heterogeneity, there is insufficient evidence to routinely recommend PRP for AC. However, the results are promising and do support considering PRP as an adjunct treatment option for AC, especially for patients refractory and/or averse to corticosteroids or alternative treatment modalities. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

DirectRMDB: a database of post-transcriptional RNA modifications unveiled from direct RNA sequencing technology.

With advanced technologies to map RNA modifications, our understanding of them has been revolutionized, and they are seen to be far more widespread and important than previously thought. Current next-generation sequencing (NGS)-based modification profiling methods are blind to RNA modifications and thus require selective chemical treatment or antibody immunoprecipitation methods for particular modification types. They also face the problem of short read length, isoform ambiguities, biases and artifacts. Direct RNA sequencing (DRS) technologies, commercialized by Oxford Nanopore Technologies (ONT), enable the direct interrogation of any given modification present in individual transcripts and promise to address the limitations of previous NGS-based methods. Here, we present the first ONT-based database of quantitative RNA modification profiles, DirectRMDB, which includes 16 types of modification and a total of 904,712 modification sites in 25 species identified from 39 independent studies. In addition to standard functions adopted by existing databases, such as gene annotations and post-transcriptional association analysis, we provide a fresh view of RNA modifications, which enables exploration of the epitranscriptome in an isoform-specific manner. The DirectRMDB database is freely available at: http://www.rnamd.org/directRMDB/.